Polyetherimide compositions and methods for the manufacture and use thereof

ABSTRACT

This disclosure relates to polyetherimide compositions whose residual phenolic monomers exhibit little or no estradiol binding activity. Also disclosed are methods for making the disclosed polyetherimides and articles of manufacture comprising the disclosed polyetherimides.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.13/564,352, filed Aug. 1, 2012, which claims the benefit of priority toU.S. Provisional Application No. 61/526,032, filed Aug. 22, 2011, whichare hereby incorporated by reference in their entirety.

FIELD OF THE INVENTION

The present disclosure relates to polyetherimide compositions having,among other characteristics, significantly reduced or even no measurablelevel of estradiol like binding activity. Also included herein aremethods for preparing and/or using the same, as well as articles formedfrom such compositions and blends

BACKGROUND OF THE INVENTION

Polyimides (PI), and in particular polyetherimides (PEI), are highperformance polymers having a glass transition temperature (Tg) ofgreater than 180° C. These polymers further have high strength, heatresistance, and modulus, and broad chemical resistance. Polyetherimidesare widely used in applications as diverse as automotive,telecommunication, aerospace, electrical/electronics, transportation,food service and healthcare. Adding a reinforcing filler helps providematerials that are particularly useful as molded parts for metalreplacement, for example in automotive and electrical/electronicapplications since these compositions offer good mechanical and thermalproperties.

However, when prepared under certain conditions, polyetherimides canhave small amounts of residual phenolic monomers. In some instancesthese impurities may correspond to the monomeric phenolic startingmaterials initially used to manufacture the polyetherimide. Besidesaffecting polymer properties, residual monomers can also be of concernin view of emerging regulatory considerations. Therefore, completeconversion of monomers is usually the desire of any polymer producer butis not always attainable. To that end, there remains a need in the artfor thermoplastic polyetherimide compositions whose residual phenolicmonomers exhibit certain beneficial characteristics. Desirablecharacteristics of such residual phenolic monomers include, amongothers, relatively little or even no estradiol binding activity.

SUMMARY OF THE INVENTION

This invention relates generally to polyetherimide compositions whoseresidual phenolic monomers, if present, exhibit relatively little oreven no estradiol binding activity. The polyetherimide compositions aremanufactured from starting materials that similarly exhibit relativelylittle or even no estradiol binding activity.

In view of the foregoing, embodiments of the invention generally providea polyetherimide composition comprising repeating units derived from oneor more phenolic monomers, wherein each of the one or more phenolicmonomers does not exhibit a half maximal inhibitory concentration (IC₅₀)less than 0.00025M for alpha or beta in vitro estradiol receptors.Additionally, when the polyetherimide is prepared under conditions wheresmall amounts of residual phenolic monomer are present with the polymer,each of the one or more residual phenolic monomers similarly does notexhibit a half maximal inhibitory concentration (IC₅₀) less than0.00025M for alpha or beta in vitro estradiol receptors.

Further embodiments of the invention also provide polymer blendscomprising the polyetherimide compositions disclosed herein.

In another embodiment, the present invention also provides variousarticles of manufacture comprising the polyetherimide compositionsdisclosed herein.

In still further embodiments, the invention provides methods for themanufacture of the disclosed polyetherimide compositions. According tosome embodiments, a method is provided that generally comprises reactingan aromatic dihydroxy monomer salt and a bis halo or bis nitrophthalimide under conditions effective to provide a polyetherimidereaction product. This type of polyetherimide polymerization process isdescribed, for example, in U.S. Pat. Nos. 5,229,482; 4,554,357;3,847,869 and 3,787,364. The aromatic dihydroxy monomer is selected suchthat it does not exhibit a half maximal inhibitory concentration (IC₅₀)less than 0.00025M for alpha or beta in vitro estradiol receptors. Theresulting polyetherimide is further characterized in that when thepolyetherimide is prepared under conditions where the aromatic dihydroxymonomer is not completely incorporated into the polymer or notsubsequently removed from the polymer, each of the one or more residualphenolic monomers does not exhibit a half maximal inhibitoryconcentration (IC₅₀) less than 0.00025M for alpha or beta in vitroestradiol receptors. In some instances the residual phenolic monomercontent will be 100 ppm or less.

According to alternative embodiments, a method is provided thatgenerally comprises reacting an aromatic bis(ether anhydride) with adiamine under conditions effective to provide a polyetherimide reactionproduct (as described, for example, in U.S. Pat. Nos. 4,585,852;4,443,592 and 4,417,044). The aromatic bis(ether anhydride) may bederived from an aromatic dihydroxy monomer salt displacing a mono haloor nitro N-alkyl phthalimide to make a bis alkyl imide aromatic ether(as described, for example, in U.S. Pat. No. 4,257,953). The bis alkylimide aromatic ether can be subsequently converted to an aromatic etherdianhydride, for example, as in U.S. Pat. Nos. 4,329,496; 4,329,292 and4,318,857. The aromatic ether dianhydrides can be reacted with aryl oralkyl diamines as described in the art (for example U.S. Pat. Nos.4,324,883; 4,324,883 and 4,293,683) to make polyetherimides. Thearomatic bis(ether anhydride) thereby derived is from an aromaticdihydroxy monomer that does not exhibit a half maximal inhibitoryconcentration (IC₅₀) less than 0.00025M for alpha or beta in vitroestradiol receptors. The resulting polyetherimide is furthercharacterized in that when the polyetherimide is prepared underconditions where the aromatic dihydroxy monomer is not completelyincorporated into the bisimide monomer or polymer, or is notsubsequently removed from the polymer, each of the one or more residualmonomers does not exhibit a half maximal inhibitory concentration (IC₅₀)less than 0.00025M for alpha and/or beta in vitro estradiol receptors.

Additional advantages will be set forth in part in the description whichfollows. The advantages will be realized and attained by means of theelements and combinations particularly pointed out in the appendedclaims. It is to be understood that both the foregoing generaldescription and the following detailed description are exemplary andexplanatory only and are not restrictive.

DETAILED DESCRIPTION OF THE INVENTION

The present invention can be understood more readily by reference to thefollowing detailed description, examples, drawings, and claims, andtheir previous and following description. However, before the presentcompositions, compounds, devices, systems, and/or methods are disclosedand described, it is to be understood that this invention is not limitedto the specific compositions, compounds, devices, systems, and/ormethods disclosed unless otherwise specified, as such can, of course,vary. It is also to be understood that the terminology used herein isfor the purpose of describing particular aspects only and is notintended to be limiting.

The following description of the invention is provided as an enablingteaching of the invention in its best, currently known embodiment. Tothis end, those of ordinary skill in the relevant art will recognize andappreciate that many changes can be made to the various aspects of theinvention described herein, while still obtaining the beneficial resultsof the present invention. It will also be apparent that some of thedesired benefits of the present invention can be obtained by selectingsome of the features of the present invention without utilizing otherfeatures. Accordingly, those of ordinary skill in the relevant art willrecognize that many modifications and adaptations to the presentinvention are possible and can even be desirable in certaincircumstances and are a part of the present invention. Thus, thefollowing description is provided as illustrative of the principles ofthe present invention and not in limitation thereof.

As used herein, the singular forms “a,” “an” and “the” include pluralreferents unless the context clearly dictates otherwise. Thus, forexample, reference to an “aromatic dihydroxy monomer” can include two ormore such monomers unless the context indicates otherwise.

Ranges can be expressed herein as from “about” one particular value,and/or to “about” another particular value. When such a range isexpressed, another aspect includes from the one particular value and/orto the other particular value. Similarly, when values are expressed asapproximations, by use of the antecedent “about,” it will be understoodthat the particular approximated value forms another aspect of theinvention. It will be further understood that the endpoints of each ofthe ranges are significant both in relation to the other endpoint, andindependently of the other endpoint.

All ranges disclosed herein are inclusive of the endpoints and areindependently combinable. The endpoints of the ranges and any valuesdisclosed herein are not limited to the precise range or value; they aresufficiently imprecise to include values approximating these rangesand/or values. Ranges articulated within this disclosure, e.g.numerics/values, shall include disclosure for possession purposes andclaim purposes of the individual points within the range, sub-ranges,and combinations thereof. As an example, for the recitation of numericranges herein, each intervening number there between with the samedegree of precision is explicitly contemplated—for the range of 6-9, thenumbers 7 and 8 are contemplated in addition to 6 and 9, and for therange 6.0-7.0, the number 6.0, 6.1, 6.2, 6.3, 6.4, 6.5, 6.6, 6.7, 6.8,6.9, and 7.0 are explicitly contemplated.

Various combinations of elements of this disclosure are encompassed bythis invention, e.g. combinations of elements from dependent claims thatdepend upon the same independent claim.

As used herein, the terms “optional” or “optionally” mean that thesubsequently described event, condition, component, or circumstance mayor may not occur, and that the description includes instances where saidevent or circumstance occurs and instances where it does not.

A weight percent of a component, unless specifically stated to thecontrary, is based on the total weight of the formulation or compositionin which the component is included.

A residue of a chemical species, as used in the specification andconcluding claims, refers to the moiety that is the resulting product ofthe chemical species in a particular reaction scheme or subsequentformulation or chemical product, regardless of whether the moiety isactually obtained from the chemical species. Thus, an ethylene glycolresidue in a polyester refers to one or more —OCH₂CH₂O-units in thepolyester, regardless of whether ethylene glycol was used to prepare thepolyester. Similarly, a sebacic acid residue in a polyester refers toone or more —CO(CH₂)₈CO— moieties in the polyester, regardless ofwhether the residue is obtained by reacting sebacic acid or an esterthereof to obtain the polyester.

Compounds are described using standard nomenclature. For example, anyposition not substituted by any indicated group is understood to haveits valency filled by a bond as indicated, or a hydrogen atom. A dash(“-”) that is not between two letters or symbols is used to indicate apoint of attachment for a substituent. For example, the aldehyde group—CHO is attached through the carbon of the carbonyl group.

The term “aliphatic” refers to a linear or branched array of atoms thatis not cyclic and has a valence of at least one. Aliphatic groups aredefined to comprise at least one carbon atom. The array of atoms mayinclude heteroatoms such as nitrogen, sulfur, silicon, selenium andoxygen or may be composed exclusively of carbon and hydrogen (“Alkyl”).Aliphatic groups may be substituted or unsubstituted. Exemplaryaliphatic groups include, but are not limited to, methyl, ethyl,isopropyl, isobutyl, chloromethyl, hydroxymethyl (—CH₂OH),mercaptomethyl (—CH₂SH), methoxy, methoxycarbonyl (CH₃OCO—), nitromethyl(—CH₂NO₂), and thiocarbonyl.

The term “alkyl group” as used herein is a branched or unbranchedsaturated hydrocarbon group of 1 to 24 carbon atoms, such as methyl,ethyl, n-propyl, isopropyl, n-butyl, isobutyl, t-butyl, pentyl, hexyl,heptyl, octyl, decyl, tetradecyl, hexadecyl, eicosyl, tetracosyl and thelike. A “lower alkyl” group is an alkyl group containing from one to sixcarbon atoms.

The term “alkoxy” as used herein is an alkyl group bound through asingle, terminal ether linkage; that is, an “alkoxy” group can bedefined as —OR where R is alkyl as defined above. A “lower alkoxy” groupis an alkoxy group containing from one to six carbon atoms.

The term “alkenyl group” as used herein is a hydrocarbon group of from 2to 24 carbon atoms and structural formula containing at least onecarbon-carbon double bond. Asymmetric structures such as (AB)C═C(CD) areintended to include both the E and Z isomers. This can be presumed instructural formulae herein wherein an asymmetric alkene is present, orit can be explicitly indicated by the bond symbol C.

The term “alkynyl group” as used herein is a hydrocarbon group of 2 to24 carbon atoms and a structural formula containing at least onecarbon-carbon triple bond.

The term “aryl group” as used herein is any carbon-based aromatic groupincluding, but not limited to, benzene, naphthalene, etc.

The term “aromatic” refers to an array of atoms having a valence of atleast one and comprising at least one aromatic group. The array of atomsmay include heteroatoms such as nitrogen, sulfur, selenium, silicon andoxygen, or may be composed exclusively of carbon and hydrogen. Thearomatic group may also include nonaromatic components. For example, abenzyl group is an aromatic group that comprises a phenyl ring (thearomatic component) and a methylene group (the nonaromatic component).Exemplary aromatic groups include, but are not limited to, phenyl,pyridyl, furanyl, thienyl, naphthyl, biphenyl, 4-trifluoromethylphenyl,4-chloromethylphen-1-yl, and 3-trichloromethylphen-1-yl (3-CCl₃Ph-).

The term “aromatic” also includes “heteroaryl group,” which is definedas an aromatic group that has at least one heteroatom incorporatedwithin the ring of the aromatic group. Examples of heteroatoms include,but are not limited to, nitrogen, oxygen, sulfur, and phosphorus. Thearyl group can be substituted or unsubstituted. The aryl group can besubstituted with one or more groups including, but not limited to,alkyl, alkynyl, alkenyl, aryl, halide, nitro, amino, ester, ketone,aldehyde, hydroxy, carboxylic acid, or alkoxy.

The term “cycloalkyl group” as used herein is a non-aromaticcarbon-based ring composed of at least three carbon atoms. Examples ofcycloalkyl groups include, but are not limited to, cyclopropyl,cyclobutyl, cyclopentyl, cyclohexyl, etc. The term “heterocycloalkylgroup” is a cycloalkyl group as defined above where at least one of thecarbon atoms of the ring is substituted with a heteroatom such as, butnot limited to, nitrogen, oxygen, sulfur, or phosphorus.

The term “aralkyl” as used herein is an aryl group having an alkyl,alkynyl, or alkenyl group as defined above attached to the aromaticgroup. An example of an aralkyl group is a benzyl group.

The term “hydroxyalkyl group” as used herein is an alkyl, alkenyl,alkynyl, aryl, aralkyl, cycloalkyl, halogenated alkyl, orheterocycloalkyl group described above that has at least one hydrogenatom substituted with a hydroxyl group.

The term “alkoxyalkyl group” is defined as an alkyl, alkenyl, alkynyl,aryl, aralkyl, cycloalkyl, halogenated alkyl, or heterocycloalkyl groupdescribed above that has at least one hydrogen atom substituted with analkoxy group described above.

The term “ester” as used herein is represented by the formula —C(O)OA,where A can be an alkyl, halogenated alkyl, alkenyl, alkynyl, aryl,heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, orheterocycloalkenyl group described above.

The term “carbonate group” as used herein is represented by the formula—OC(O)OR, where R can be hydrogen, an alkyl, alkenyl, alkynyl, aryl,aralkyl, cycloalkyl, halogenated alkyl, or heterocycloalkyl groupdescribed above.

The term “carboxylic acid” as used herein is represented by the formula—C(O)OH.

The term “aldehyde” as used herein is represented by the formula —C(O)H.

The term “keto group” as used herein is represented by the formula—C(O)R, where R is an alkyl, alkenyl, alkynyl, aryl, aralkyl,cycloalkyl, halogenated alkyl, or heterocycloalkyl group describedabove.

The term “carbonyl group” as used herein is represented by the formulaC═O.

The term “integer” means a whole number and includes zero. For example,the expression “n is an integer from 0 to 4” means n may be any wholenumber from 0 to 4, including 0.

As used herein, the term half maximal inhibitory concentration (IC₅₀) isa quantitative measure that indicates how much of a particularsubstance, i.e., an inhibitor, is needed to inhibit a given biologicalprocess or component of a process, by one half. In other words, it isthe half maximal (50%) inhibitory concentration (IC) of a substance (50%IC, or IC₅₀). It is commonly known to one of ordinary skill in the artand used as a measure of antagonist drug potency in pharmacologicalresearch. The (IC₅₀) of a particular substance can be determined usingconventional competition binding assays. In this type of assay, a singleconcentration of radioligand (such as an agonist) is used in every assaytube. The ligand is used at a low concentration, usually at or below itsK_(d) value. The level of specific binding of the radioligand is thendetermined in the presence of a range of concentrations of othercompeting non-radioactive compounds (usually antagonists), in order tomeasure the potency with which they compete for the binding of theradioligand. Competition curves may also be computer-fitted to alogistic function as described under direct fit. The IC₅₀ is theconcentration of competing ligand which displaces 50% of the specificbinding of the radioligand.

As summarized above, the present invention provides polyetherimidecompositions comprising repeating units derived in part from one or morearomatic dihydroxy monomers. The aromatic dihydroxy monomers used in thepreparation of the polyetherimides exhibit relatively little or even nomeasurable estradiol binding activity as characterized by their halfmaximal inhibitory concentration (IC₅₀) for alpha or beta in vitroestradiol receptors. Specifically, according to some embodiments, thearomatic dihydroxy monomers of the invention do not exhibit a halfmaximal inhibitory concentration (IC₅₀) less than 0.00025M for alpha orbeta in vitro estradiol receptors. According to further embodiments,each of the one or more aromatic dihydroxy monomers do not exhibit ahalf maximal inhibitory concentration (IC₅₀) less than 0.0003M,0.00035M, 0.0004M, 0.00045M, 0.0005M, 0.00075M, or even 0.001M, foralpha or beta in vitro estradiol receptors. In still other embodiments,aromatic dihydroxy monomers do not exhibit any identifiable half maximalinhibitory concentration (IC₅₀) greater than or equal to about 0.00025M,0.0003M, 0.00035M, 0.0004M, 0.00045M, 0.0005M, 0.00075M, or even 0.001M,for alpha and/or beta in vitro estradiol receptors.

According to some embodiments, aromatic dihydroxy monomers suitable foruse in the polyetherimides of the invention include phenolic monomers.These phenolic monomers can comprise dihydric phenols (also known asbisphenols), mono phenols, or a combination thereof. To that end,specific examples of suitable phenolic monomers include, withoutlimitation, resorcinol, hydroquinone, methyl hydroquinone, t-butylhydroquinone, di-t-butyl hydroquinones (DTBHQ), biphenols, tetramethylbisphenol-A, spiro biindane bisphenols (SBIBP), bis-(hydroxyaryl)-N-aryl isoindolinones, or any combination thereof. It should beunderstood that, in view of this disclosure, any additional suitablearomatic dihydroxy monomers exhibiting a lack of estradiol bindingactivity characterized by the half maximal inhibitory concentrationvalues described above can be used.

As will be appreciated upon practice of the present invention, when thedisclosed polyetherimides are subjected to very abusive conditions wherethe formation of one or more degradation products might occur, theresulting degradants or other chemical species if formed through anabusive degradation process will similarly exhibit relatively little oreven no measurable estradiol binding activity as characterized by thehalf maximal inhibitory concentration (IC₅₀) for alpha or beta in vitroestradiol receptors. For example, according to some embodiments,degradants of the disclosed polyetherimides will not exhibit a halfmaximal inhibitory concentration (IC₅₀) less than 0.00025M for alpha orbeta in vitro estradiol receptors. According to further embodiments,degradants of the disclosed polyetherimides do not exhibit a halfmaximal inhibitory concentration (IC₅₀) less than 0.0003M, 0.00035M,0.0004M, 0.00045M, 0.0005M, 0.00075M, or even 0.001M, for alpha or betain vitro estradiol receptors. In still other embodiments, degradants ofthe disclosed polyetherimides do not exhibit any identifiable halfmaximal inhibitory concentration (IC₅₀) greater than or equal to about0.00025M, 0.0003M, 0.00035M, 0.0004M, 0.00045M, 0.0005M, 0.00075M, oreven 0.001M, for alpha and/or beta in vitro estradiol receptors.

As will also be appreciated upon practice of the present invention, anyresidual monomer content of the disclosed polyetherimides will exhibitthe half maximal inhibitory concentration (IC₅₀) values of the aromaticdihydroxy monomers described above. For example, according to someembodiments, any residual monomer content of the disclosedpolyetherimides will not exhibit a half maximal inhibitory concentration(IC₅₀) less than 0.00025M for alpha or beta in vitro estradiolreceptors. According to further embodiments, any residual monomercontent of the disclosed polyetherimides do not exhibit a half maximalinhibitory concentration (IC₅₀) less than 0.0003M, 0.00035M, 0.0004M,0.00045M, 0.0005M, 0.00075M, or even 0.001M, for alpha or beta in vitroestradiol receptors. In still other embodiments, any residual monomercontent of the disclosed polyetherimides do not exhibit any identifiablehalf maximal inhibitory concentration (IC₅₀) greater than or equal toabout 0.00025M, 0.0003M, 0.00035M, 0.0004M, 0.00045M, 0.0005M, 0.00075M,or even 0.001M, for alpha and/or beta in vitro estradiol receptors. Tothat end, according to embodiments of the invention, the disclosedpolyetherimides comprise a residual monomer content that is preferablyless than 100 ppm. According to still further embodiments, the disclosedpolyetherimide comprise a residual monomer content less than 95 ppm, 90ppm, 85, ppm, 80 ppm, 75 ppm, 70 ppm, 65 ppm, 60 ppm, 55 ppm, or eventless than 50 ppm. Of course, in still further embodiments, the disclosedpolysulfones contain essentially no residual monomer content. In someinstances the residual phenolic monomer will be present in thepolyetherimide polymer some number greater than zero and less than orequal to 1,000 ppm based on the polyetherimide polymer. In otherinstances the residual phenolic monomer will be present in thepolyetherimide polymer at 0.1 to 1,000 ppm. In yet other instances theresidual phenolic monomer will be present in the polyetherimide polymerat 1 to 1,000 ppm.

The disclosed polyetherimides can be synthesized by any conventionallyknown process for the manufacture of a polyetherimide. For example, andwithout limitation, the disclosed polyetherimides can be prepared by aconventional displacement polymerization reaction whereby a halo ornitro substituted bis phthalamide, such as a bis 4-chloro phthalimide, bis 4-fluoro phthalimide or bis 4-nitro phthalimide is reacted with adianion salt of a disclosed aromatic dihydroxy compound under conditionseffective to result in the desired polymerization. These displacementpolymerizations are facilitated by the use of a phase transfer catalystsuch a tetra butyl ammonium chloride, tetra phenyl phosphonium bromide,hexa ethyl guanidinium chloride or other conventionally known phasetransfer catalysts. In other instances polyetherimde polymerization maybe conducted in an aprotic polar solvent. In these displacementpolymerization reactions the resulting resin can also be end capped tocontrol molecular weight. Exemplary and non-limiting endcapping agentsthat can be used include mono chloro phthalimides or mono phenols. Asdescribed in further detail below, according to some embodiments, apreferred endcapping agent is phenol due to its lack of estradiolbinding activity. In particular, phenol does not exhibit a half maximalinhibitory concentration (IC₅₀) less than 0.00025M for alpha or beta invitro estradiol receptors

Substituted bis phthalamides suitable for reacting with the dianion saltof a disclosed aromatic dihydroxy compound in a displacementpolymerization can themselves be synthesized by any conventionally knownprocess. According to some embodiments, such bis phthalimides can beselected from those bis phthalimides represented by the followingstructure:

Linkage T in formula (I) includes substituted or unsubstituted divalentorganic radicals such as (a) aromatic hydrocarbon radicals having about6 to about 20 carbon atoms and halogenated derivatives thereof; (b)straight or branched chain alkylene radicals having about 2 to about 20carbon atoms; (c) cycloalkylene radicals having about 3 to about 20carbon atoms, or (d) divalent radicals of the general formula (II)

wherein Q includes a divalent moiety selected from the group consistingof —O—, —S—, —C(O)—, —SO2-, —SO—, -CyH2y- (y being an integer from 1 to5), and halogenated derivatives thereof, including perfluoroalkylenegroups. In a specific exemplary embodiment, linkage T represents aphenylene moiety, such as m-phenylene, which as one of ordinary skill inthe art will understand, can be derived from m-phenylene diamine (mPD).Alternatively, in another specific and only exemplary embodiment,linkage T represents a diphenyl sulfone, which as one of ordinary skillin the art will again understand, can be derived from diamine diphenylsulfone (DDS). With further reference to formula (I), the substituent Rincludes halogen or nitro. The substituents R are beneficially locatedin the 3,3′, 3,4′, 4,3′, or 4,4′ positions, and mixtures thereof.

In a second exemplary method, the disclosed polyetherimdes can beprepared by the reaction of an aromatic bis(ether anhydride) of theformula (III) with a stoichiometric amount of a diamine. The aromaticbis(ether anhydride) can be selected from the group represented by thefollowing structure:

wherein linkage Z represents an aryl diether linkage of the generalformula —O—Z′—O— derived from the disclosed aromatic dihydroxycompounds: including for example resorcinol, hydroquinone, methylhydroquinone, t-butyl hydroquinone, di-t-butyl hydroquinones, biphenols,tetramethyl bisphenol-A, spiro biindane bisphenols, bis-(hydroxyaryl)-N-aryl isoindolinones or any combination thereof. Preferrably, thedivalent bonds of the —O—Z′—O— group are located in the 3,3′, 3,4′,4,3′, or the 4,4′ positions. The bis(ether anhydride)s can, for example,be prepared by the hydrolysis, followed by dehydration, of the reactionproduct of a nitro substituted phenyl dinitrile with a metal salt of adisclosed aromatic dihydroxy compound in the presence of a dipolar,aprotic solvent. The ether dianhydrides can also be prepared by exchangeof a bis imide with an anhydride, for instance phthalic anhydride. Thepolyetherimde may also be end capped with either aniline or phthalicanhydride.

Diamines that are well suited for polymerization with theabove-described aromatic bis(ether anhydrides) include those representedby the formula:H₂N—Y—NH₂  (IV),wherein Y in formula (IV) represents substituted or unsubstituteddivalent organic radicals such as (a) aromatic hydrocarbon radicalshaving about 6 to about 20 carbon atoms and halogenated derivativesthereof; (b) straight or branched chain alkylene radicals having about 2to about 20 carbon atoms; (c) cycloalkylene radicals having about 3 toabout 20 carbon atoms, or (d) divalent radicals of the general formula(II) as defined above. In a specific exemplary and non-limitingembodiment, a preferred amines for reacting with the disclosed aromaticbis(ether anhydrides) are aryl amines including m-phenylene diamine(mPD) and p-phenylene diamine (pPD). Alternatively, in another specificand only exemplary embodiment, a preferred aryl amine for reacting withthe disclosed aromatic bis(ether anhydrides) includes diamino diphenylsulfone (DDS). Such a polymer is a polyetherimide sulfone. Mixtures ofdiamines may also be employed. The substituents R are beneficiallylocated in the 3,3′, 3,4′, 4,3′, or 4,4′ positions, and mixturesthereof.

The polyetherimides of the present invention can be provided ashomopolymers comprising repeating units derived from a single aromaticdihydroxy monomer. Alternatively, in other embodiments, thepolyetherimides of the invention can be provided as co-polyetherimides,comprising repeating units derived from two or more aromatic dihydroxymonomers or two or more diamines as described herein. According to theseembodiments, it should be understood that the disclosedco-polyetherimides can be formulated to provide any desired relativemole ratio of repeating units within the chain of co-polyetherimides.

The relative mole ratio among the various monomeric components presentin a copolymer will depend, in part, upon the total number of differingmonomeric components present. The mole ratios can be expressed asrelative mole percentages whereby the total mole percentage of monomericcomponents adds up to 100 mole %. For example, a copolymer comprising afirst aromatic dihydroxy monomer and a second aromatic dihydroxy monomercan be provided wherein the relative mole percentage ratio of the firstmonomer to the second monomer is 90 mole % to 10 mole %, 80 mole % to 20mole %, 75 mole % to 25 mole %, 70 mole % to 30 mole %, 60 mole % to 40mole %, or even 50 mole % to 50 mole %. Polyetherimide homopolymers andcopolymers may be blended separately or together in any combination.

In addition to the structural units described above, it is furthercontemplated that the polyetherimides of the present invention cancomprise one or more non-polyetherimide additives. Preferably, the oneor more non-polyetherimide additive also does not exhibit a half maximalinhibitory concentration (IC₅₀) less than 0.00025M for alpha or beta invitro estradiol receptors. To that end, exemplary and non-limitingadditives that can be incorporated into the polyetherimides includestabilizers, antioxidants, colorants, impact modifiers, flameretardants, branching agents, anti drip additives, mold releaseadditives, lubricants, plasticizers, minerals (such as talc, clay,milled glass or glass spheres), reinforcement additives such as carbonor glass fibers, or any combination thereof. The amount of any suchadditive that can be used is that amount sufficient to result in thedesired degree or effect for which the additive is intended. Forexample, if the additive is an antioxidant, color stabilizer or flameretardant the amount of additive will be that amount sufficient toprovide a desired level of intended performance e.g. resistance tothermal aging, lower color or resistance to ignition. Such amounts canbe readily determined by one of ordinary skill in the art without undueexperimentation.

Any one or more of the above referenced non-polyetherimide additives canbe provided as a phosphorous containing compound. Exemplary phosphorouscontaining compounds including phosphites and phosphonates or mixturesthereof. Thus, according to embodiments of the invention wherephosphorous containing additives are present, it is preferable that theparticular phosphorous containing additive similarly does not exhibit ahalf maximal inhibitory concentration (IC₅₀) less than 0.00025M foralpha or beta in vitro estradiol receptors. To that end, when suchphosphorous containing additives are subjected to a hydrolysis reactionunder conditions effective to provide one or more hydrolysis products,the hydrolysis product will similarly not exhibit a half maximalinhibitory concentration (IC₅₀) less than 0.00025M for alpha or beta invitro estradiol receptors.

According to embodiments of the invention, suitable phosphite additivesinclude diphenyl alkyl phosphites, phenyl dialkyl phosphites, trialkylphosphites, dialkyl phosphites, triphenyl phosphites, diphenylpentaerythritol diphosphite, or any combination thereof. The phosphiteadditives can be present in any desired or effective amount, when usedthe phosphite additives are preferably present in an amount in the rangeof from 0.00001 to 0.3 wt % phosphite, 0.00001 to 0.2 wt % phosphite, oreven in the range of from 0.0001 to 0.01 wt % phosphite. Still further,it should be understood that a phosphorous containing additive such as aphosphite additive can have any desired molecular weight. However,according to a preferred embodiment, the phosphite additive has amolecular weight that is greater than 200 Daltons.

Conventional polymerization processes for manufacturing polyetherimidesalso commonly employ the use of a chain stopper (also referred to as anendcapping agent) during the polymerization reaction. The chain stopperlimits molecular weight growth rate, and thus can be used to controlsmolecular weight in the polyetherimide. To that end, many conventionallyknown end capping agents exhibit undesirably high levels of estradiolbinding activity. In contrast, however, suitable end capping agents orchain stoppers for use with the present invention exhibit estradiolbinding activity levels similar or even identical to that of theselected aromatic dihydroxy monomers. More specifically, the end cappingagents suitable for use in the present invention also do not exhibit ahalf maximal inhibitory concentration (IC₅₀) less than 0.00025M foralpha or beta in vitro estradiol receptors. As such, any potentialdegradation product of the selected chain stopper, if formed, willlikewise not exhibit a half maximal inhibitory concentration (IC₅₀) lessthan 0.00025M for alpha or beta in vitro estradiol receptors. Exemplarychain stoppers include certain mono amines (for example aniline), monoanhydrides (for example phthalic anhydride), mono-phenolic compounds andthe like. In one embodiment, a suitable chain stopper for use in thepresent invention is phenol. Thus, when phenol is included as a chainstopper, the resulting polyetherimide comprises phenol as an end cap tothe polymer chain. It should be understood however that thepolyetherimides disclosed herein can be produced having any desiredweight average molecular weight (Mw) with any end cap.

The disclosed polyetherimides can have any desired molecular weight. Forexample, disclosed polyetherimides can have weight average molecularweights in the range of from 3,000 to 80,000 Daltons, includingexemplary molecular weights of 5,000, 7,000, 10,000, 15,000, 20,000,25,000, 30,000, 35,000, 40,000 and 45,000, 50,000, 55,000, 60,000 and65,000, 70,000 and 75,000. In still further examples, the weight averagemolecular weight (Mw) of a disclosed polyetherimides can be in a rangeof from any one of the above mentioned values to any other of the abovementioned values. For example, molecular weight of a disclosedpolyetherimides can be in the range of from 3,000 to 80,000 Daltons. Instill a further example, the molecular weight of a disclosedpolyetherimides can be expressed as a value less than any one of theabove disclosed values or, alternatively, can be expressed as a valuegreater than any one of the above disclosed values. For example, themolecular weight of a disclosed polyetherimides can be greater than3,000 Daltons, or less than 80,000 Daltons. Molecular weight may bedetermined by gel permeation chromatography (GPC) as described, forexample, in American Society for Testing Materials (ASTM) method D5296.

As used in the specification and claims herein, the term “compounding”refers to the intimate mixing of the polyetherimide andnon-polyetherimide additives such as the phosphorous containing compoundprior to preparation of a final product or article. Compounding iscommonly performed by combining as-synthesized polyetherimide with theadditive(s) and passing the mixture through an extruder to producecompounded pellets that can be dried and then further processed, forexample into shaped articles. When dried, the pellets preferably have amoisture content less than about 100 ppm. Low moisture content is veryimportant for formation of molded articles (especially injection moldedarticles) free from bubbles, voids or surface imperfections such assplay. Exemplary further melt processing can include injection molding,blow molding, extrusion, gas assist molding or compression moldingprocesses. The additive(s) can be combined with the as-synthesizedpolyetherimide prior to any pelletizing, or after pelletization of theas-synthesized polyetherimide.

Compounding can be performed either in a melt or in solution. In themelt, the polyetherimide and additives can be melt mixed or kneadedtogether in an extruder, melt kneader, reactor or other system or devicecapable of melting and mixing the polyetherimide and the additives,followed by extrusion or pelletization, or by direct melt processinginto shaped articles. In solution processing, the polyetherimide andadditive(s) are combined in an inert solvent and maintained together forsufficient reaction time and temperature to reduce the color of thecomposition. The solvent is then removed, for example using vacuum. Insome instances residual solvent for example chlorobenzene,o-dichlorobenzene, sulfolane, anisole or veratrole, should be less than100 ppm. In other instances residual solvent will be less than 50 ppm.

The temperature of the extruder in the foregoing methods will generallybe the conventional extruder temperature used for forming pellets of aparticular thermoplastic polyetherimide. The appropriate extrudertemperature will depend on the properties of both the polyetherimide andthe additives. Higher molecular weight polyetherimides and/or high heatpolyetherimides containing monomer units that increase the glasstransition temperature of the polyetherimide will typically requirehigher extruder temperatures, so that the melt viscosity is low enoughfor sufficient mixing with the additives to occur. Suitable temperatureranges are 300 to 420° C., specifically 330 to 370° C. One skilled inthe art will understand that the temperature of the polymer melt canvary somewhat from the extruder temperature depending on the occurrenceof exothermic and/or endothermic reactions and processes and any heatgenerated by the mechanical mixing of the molten polymer.

The polyetherimide compositions of the invention can further be blendedwith additional thermoplastic resins or polymers. For example, andwithout limitation, the polyetherimides of the invention can be blendedwith polycarbonates, polyester carbonates, polyarylates, polyamides,polyphenylene sulfides, polyphenylene ethers, polyesters, polysulfones,polyethersulfones, polyphenylene ether sulfones, polyolefins, or anycombination thereof.

In some instance the disclosed polyetherimides may exhibit a phenolicgroup content less than 20 meq/kg; a chloride content less than 20 ppm;a transition metal content less than 20 ppm; and a residual monomercontent less than 100 ppm. Residual monomer content can be measuredusing standard techniques, such as gas or liquid chromatography, on anextract of the polymer. The extract can also be titrated to determinephenolic content. Chloride content can be determined for example byanalysis of an aqueous extract of the polymer using for example ionchromatography (IC). Metals, including transition metals, and totalchloride can be determined by pyrolysis/ashing of the sample followed byion plasma chromatography (ICP) or other known techniques. Phenolic endgroups of the polymer may be measured by known techniques such astitration, infrared spectroscopy (IR), and nuclear magnetic resonance(NMR). In one instance ³¹P NMR analysis using phosphorousfunctionalization of end groups can be used to characterize the resins.Wherein the polyetherimide (PEI) resin was dissolved in CDCl₃ withpyridine and chromium acetylacetonate (CrAcAc) and the phenolic hydroxylgroups are phosphorylated with o-phenylene phosphoro chloridite toenhance the NMR signal.

In other instances the polyetherimide will have a Tg from 200 to 320°C., a weight gain on immersion in water for 24 hrs at 23° C. of lessthan 3.5% and a coefficient of expansion (CTE) from 30 to 50 ppm/° C.

The polyetherimides of the present invention are well suited for avariety of uses, including the manufacture of various articles. Forexample, and without limitation, the polyetherimide compositions of theinvention can be used as either clear or opaque resins for medical uses,food service uses, housewares, electronics, packaging, computerenclosures, trays, drinking glasses, pitchers, syringes, connectors,filter housings, pipes, cell phone housings, keycaps, handles, bottles,films, coatings, and the like. In some instances articles can be formedby melt processing such as injection molding, extrusion or blow molding.

Specific non-limiting examples of polyetherimide compositions of theinvention are illustrated below. In one embodiment, a polyetherimide isdisclosed wherein the repeating units are derived from the reaction ofthe bis 4-chloro phthalimide of m-phenylene with di-tert butylhydroquinone. Phenol can also be selected as the desired chain stopper.The resulting polyetherimide structure is shown below, wherein “n” canbe any desired integer based upon the desired chain length for theco-polyetherimide.

It is contemplated that this exemplified polyetherimide, and othersdisclosed herein, can be obtained having a Mw in the range of from 3,000to 80,000 Daltons; a phenolic group content less than 20 meq/kg; achloride content less than 100 ppm; a transition metal content less than20 ppm; and a residual monomer content less than 100 ppm.

In another embodiment, a polyetherimide is disclosed wherein therepeating units are derived from the reaction of the bis 4-chlorophthalimide of m-phenylene with spiro biindane bisphenol (SBIBP). Phenolcan again be selected as the desired chain stopper. The resultingpolyetherimide structure is shown below, wherein “n” can be any desiredinteger based upon the desired chain length for the polyetherimide.

It is contemplated that this exemplified polyetherimide, and othersdisclosed herein, can be obtained having a Mw in the range of from 3,000to 80,000 Daltons; a phenolic group content less than 20 meq/kg; achloride content less than 100 ppm; a transition metal content less than20 ppm; and a residual monomer content less than 100 ppm.

In another embodiment, a polyetherimide is disclosed wherein therepeating units are derived from the reaction of the bis 4-chlorophthalimide of m-phenylene with resorcinol. Phenol can again be selectedas the desired chain stopper. The resulting polyetherimide structure isshown below, wherein “n” can be any desired integer based upon thedesired chain length for the polyetherimide.

It is contemplated that this exemplified polyetherimide, and othersdisclosed herein, can be obtained having a Mw in the range of from 3,000to 80,000 Daltons; a phenolic group content less than 20 meq/kg; achloride content less than 100 ppm; a transition metal content less than20 ppm; and a residual monomer content less than 100 ppm.

In still another embodiment, a polyetherimide is disclosed wherein therepeating units are derived from the reaction of the bis 4-chlorophthalimide of m-phenylene with N-phenyl phenolphthalein bisphenol.Phenol can again be selected as the desired chain stopper. The resultingpolyetherimide structure is shown below, wherein “n” can be any desiredinteger based upon the desired chain length for the polyetherimide.

It is contemplated that this exemplified polyetherimide, and othersdisclosed herein, can be obtained having a Mw in the range of from 3,000to 80,000 Daltons; a phenolic group content less than 20 meq/kg; achloride content less than 100 ppm; a transition metal content less than20 ppm; and a residual monomer content less than 100 ppm.

In still further embodiments, a polyetherimide is disclosed wherein therepeating units are derived from the reaction of the bis 4-chlorophthalimide of diamino diphenyl sulfone with resorcinol. Phenol canagain be selected as the desired chain stopper. The resultingpolyetherimide structure is shown below, wherein “n” can be any desiredinteger based upon the desired chain length for the polyetherimide.

It is contemplated that this exemplified polyetherimide, and othersdisclosed herein, can be obtained having a Mw in the range of from 3,000to 80,000 Daltons; a phenolic group content less than 20 meq/kg; achloride content less than 100 ppm; a transition metal content less than20 ppm; and a residual monomer content less than 100 ppm.

In still another embodiment, a co-polyetherimide is disclosed whereinthe repeating units are derived from the reaction of the bis 4-chlorophthalimide of diamino diphenyl sulfone with spiro biindane bisphenol(SBIBP). Phenol can again be selected as the desired chain stopper. Theresulting polyetherimide structure is shown below, wherein “n” can beany desired integer based upon the desired chain length for theco-polyetherimide.

It is contemplated that this exemplified co-polyetherimide, and othersdisclosed herein, can be obtained having a Mw in the range of from 3,000to 80,000 Daltons; a phenolic group content less than 20 meq/kg; achloride content less than 100 ppm; a transition metal content less than20 ppm; and a residual monomer content less than 100 ppm.

In yet another embodiment, a co-polyetherimide is disclosed wherein therepeating units are derived from the reaction of the bis 4-chlorophthalimide of m-phenylene diamine with resorcinol and di t-butylhydroquinone. Phenol can again be selected as the desired chain stopper.The resulting polyetherimide structure is shown below, wherein “n” canbe any desired integer based upon the desired chain length for theco-polyetherimide.

It is contemplated that this exemplified co-polyetherimide, and othersdisclosed herein, can be obtained having a Mw in the range of from 3,000to 80,000 Daltons; a phenolic group content less than 20 meq/kg; achloride content less than 100 ppm; a transition metal content less than20 ppm; and a residual monomer content less than 100 ppm.

In a further embodiment, a co-polyetherimide is disclosed wherein therepeating units are derived from the reaction of the bis 4-chlorophthalimide of diamino diphenyl sulfone with spiro biindane bisphenoland resorcinol. Phenol can again be selected as the desired chainstopper. Other end groups are also contemplated. The resultingpolyetherimide structure is shown below, wherein “n” can be any desiredinteger based upon the desired chain length for the co-polyetherimide.

It is contemplated that this exemplified co-polyetherimide, and othersdisclosed herein, can be obtained having a Mw in the range of from 3,000to 80,000 Daltons; a phenolic group content less than 20 meq/kg; achloride content less than 100 ppm; a transition metal content less than20 ppm; and a residual monomer content less than 100 ppm.

EXAMPLES

The following examples are put forth so as to provide those of ordinaryskill in the art with a complete disclosure and description of how themethods, devices, and systems disclosed and claimed herein are made andevaluated, and are intended to be purely exemplary and are not intendedto limit the disclosure. Efforts have been made to ensure accuracy withrespect to numbers (e.g., amounts, temperature, etc.), but normalexperimental deviations should be accounted for. Unless indicatedotherwise, parts are parts by weight, temperature is in C or is atambient temperature, and pressure is at or near atmospheric. Examples ofthe invention are designated by numbers, control experiments aredesignated by letters.

Utilizing a conventional in vitro competitive binding assay as describedabove, estradiol binding activity was quantified by the half maximalinhibitory concentration (IC₅₀) value, which was evaluated for variousphenolic compounds capable for use as component starting materials inthe manufacture of polyetherimide compositions. These component startingmaterials might remain in the polymer during polymerizations run undercertain conditions as resdival monomers. Specifically, (IC₅₀) bindingconcentrations for the alpha or beta in vitro estradiol receptors forvarious compounds were tested. Three separate sets of tests were runusing a standard competitive binding assay. Samples were dissolved ineither ethanol or DMSO. The various phenolic compounds were then testedat up to seven different concentrations for each test phenolic compound.Each of those tests was run in triplicate. Tests were conducted bydisplacement of a radio-ligand. For each set of tests a 17b-estradiolcontrol sample was run to ensure proper binding of the natural hormoneunder the test conditions.

The polyetherimide hydrolysis product to be tested (Tables 1 to 3) wasinvestigated as to its binding affinity for recombinant human estradiolreceptors (rhER) alpha (α) and beta 1 (β1) in vitro. 17β-Estradiol (E₂)was used a standard whose relative binding affinity was defined as 100%.Competitive binding assays were performed by incubating rhER alpha (α)and beta 1 (β1) receptors with 10 nM [³H]estradiol (the radio ligand) inthe presence or absence of increasing concentrations, 0.25 to 250,000nM, of the phenolic test compounds of Tables 1 to 3 (nM is nano molar).Each data point is the average of at least two assays. Stock solutionsof the compounds of Tables 1 to 3 were prepared at 10×E-2 M in 100%ethanol, water or DMSO (dimethyl sulfoxide). Compounds were diluted 10fold in binding buffer and then 1:4 in the final assay mix. The finalconcentration of ethanol or DMSO in the assay well was 5%. The highestconcentration of the hydrolysis test compound was 2.5×E-4 M (250,000nM). The residual monomers of Tables 1 to 3 were tested at sevenconcentrations over log increments. The lowest concentration was2.5×E-10 M (0.25 nM). The IC₅₀ is the concentration of test substance atwhich about 50% of the radio labeled estradiol was displaced from theestradiol receptor.

In some very surprising instances (see Tables 1 to 3) the disparatephenolic compounds: tetra methyl bisphenol-A (TMBPA), phenol, N-phenylphenolphthalein bisphenol (PPPBP), resorcinol, biphenol (BP), spirobiindane bisphenol (SBIBP), di t-butyl hydroquinone (DTBHQ) and methylhydroquinone (MHQ) show no estradiol binding, even at the highestconcentration. In terms of their ability to bind to alpha or betaestradiol hormone receptors these phenolic compounds show a surprisingreduction in activity. In some instances no binding can be measuredusing standard biochemical analysis techniques to test estradiol bindingactivity. That is even at a concentration of 2.5×E-4 M there was nodisplacement of estradiol. Note that 17b-estradiol binds at very lowconcentrations of 1.0 to 14.7×E-9 M in our various control experimentsand is much more active than any of the phenolic compounds tested.

The (IC₅₀) values obtained from these experiments are provided in thetables below. As shown, many mono and bisphenols show an undesired highlevel of receptor binding. However very surprisingly the preferredphenolic compounds utilized to prepare the polyetherimide compositionsof the invention (tetra methyl bisphenol-A (TMBPA), phenol, N-phenylphenolphthalein bisphenol (PPPBP), resorcinol, biphenol (BP), spirobiindane bisphenol (SBIBP), di t-butyl hydroquinone (DTBHQ) and methylhydroquinone (MHQ)) either did not show any detectable estradiol bindingin these tests or, at a minimum, did not exhibit an (IC₅₀) bindingconcentrations less than 2.5×E-4 M. An entry of >2.5×E-4 for compoundsin Tables 1 to 3 indicates that those compounds did not compete to theextent of 50% with radio labeled 17b-estradiol at the highestconcentration (250,000 nM) tested. There was no estradiol displacementand hence no IC50 could be determined. The IC50, if identifiable at all,may be some value greater than 2.5×E-4M.

The estradiol displacement experiments of set 1 (Table 1) show that thephenolic compounds; p-cumyl phenol (control example B), dihydroxydiphenyl ether (control example C), bisphenol acetophenone (controlexample D), dimethyl acetophenone bisphenol (control example E),diphenolic acid methyl ester (control example F) and dimethyl cyclohexylbisphenol (control example G) all displace estradiol at lowconcentrations. Surprisingly, under the same conditions, tetra methylBPA (Example 1), phenol (Example 2), N-phenyl phenolphthalein bisphenol(Example 3) and resorcinol (Example 4) show no detectible estradioldisplacement at either the alpha or beta receptor at as high as 2.5×E-4molar concentration.

TABLE 1 Table 1: Experimental Set 1 IC50 rhER IC50 rhER ExampleCompounds alpha beta A 17b-estradiol control 1.0 × E−9 8.2 × E−9 Bp-Cumyl Phenol 1.4 × E−4 9.8 × E−6 (CAS# 599-64-4) C Dihydroxy DiphenylEther 6.0 × E−5 1.4 × E−5 (CAS# 1965-09-9) D Bisphenol Acetophenone 1.2× E−5 1.4 × E−6 (CAS# 1571-75-1) E Dimethyl Acetophenone 4.8 × E−6 3.5 ×E−6 Bisphenol (CAS# 4754-63-6) F Diphenolic Acid Methyl Ester 1.9 × E−51.1 × E−5 (CAS# 7297-85-0) G Dimethyl Cyclohexyl Bisphenol 1.3 × E−6 3.1× E−6 (CAS# 2362-14-3) 1 Tetra Methyl BPA >2.5 × E−4  >2.5 × E−4  (CAS#5613-46-7) 2 Phenol (CAS# 108-95-2) >2.5 × E−4  >2.5 × E−4  3 N-PhenylPhenolphthalein >2.5 × E−4  >2.5 × E−4  Bisphenol (CAS# 6607-41-6) 4Resorcinol (CAS# 108-46-3) >2.5 × E−4  >2.5 × E−4  IC50 is the conc. ofthe candidate that displaces 50% of the radioactive ligand from the rhERcells >2.5 × E4 compounds did not compete to the extent of 50% withradiolabeled 17B-estradiol at the highest conc. (250,000 nM) tested, noIC50 can be determined

In a second set of experiments (Table 2) phenolic compounds structurallysimilar to, but not identical to those of set 1, were tested as to theirability to displace estradiol. The surprising and unpredictable trend ofestradiol displacement is again observed. The bis phenolic compounds:fluorenone bis o-cresol (control example I), hydro isophorone bisphenol(control example J), bisphenol M (control example K), and bis hydroxyphenyl menthane (control example L) all displace estradiol at lowconcentrations. On the other hand, spiro biindane bisphenol (Example 5),biphenol (Example 6) and di t-butyl hydroquinone (Example 7) all show nodisplacement of the estradiol at the alpha receptor at 2.5×E-4 Mconcentration. Examples 5 and 7 also show no displacement at the betareceptor. 17b-Estradiol (control example H) binds at a very lowconcentration.

TABLE 2 Table 2: Experimental Set 2 IC50 rhER IC50 rhER ExampleCompounds alpha beta H 17b-estradiol control 7.0 × E−9 6.6 × E−9 IFluorenone Bis-o-Cresol 9.7 × E−6 2.5 × E−5 (CAS# 88938-12-9) J HydroIsophorone Bisphenol 4.5 × E−7 1.1 × E−6 (CAS# 129188-99-4) K BisphenolM 2.1 × E−6 1.4 × E−6 (CAS# 13595-25-0) L Bis Hydroxy Phenyl Menthane4.9 × E−7 6.7 × E−7 (CAS# 58555-74-1) 5 Spiro Biindane Bisphenol >2.5 ×E−4  >2.5 × E−4  (CAS# 1568-80-5) 6 Biphenol >2.5 × E−4  1.7 × E−6 (CAS#92-88-6) 7 Di t-Butyl Hydroquinone >2.5 × E−4  >2.5 × E−4  (CAS#88-58-4) IC50 is the conc. of the candidate that displaces 50% of theradioactive ligand from the rhER cells >2.5 × E4 compounds did notcompete to the extent of 50% with radiolabeled 17B-estradiol at thehighest conc. (250,000 nM) tested, no IC50 can be determined

In yet another set of experiments (Table 3) undesirable estradioldisplacement at low concentration is observed for the bisphenolsbenzophenone bisphenol (control example N) and phenolphthalein (controlexample O) while methyl hydroquinone (Example 8) surprisingly shows noalpha or beta estradiol displacement at as high as 2.5×E-4 molarconcentration. As in the other sets of experiments (Tables 1 to 3) anestradiol control (example M) was run as part of the set to establish abaseline of estradiol displacement. Estradiol displaces at much lowerconcentration than any of the phenolic compounds.

TABLE 3 Table 3: Experimental Set 3 IC50 rhER IC50 rhER ExampleCompounds alpha beta M 17b-estradiol control 10.0 × E−9  14.7 × E−9  NBenzophenone bisphenol 3.1 × E−5 3.2 × E−6 (CAS# 611-99-4) OPhenolphthalein 3.7 × E−6 1.4 × E−5 (CAS# 77-09-8) 8 MethylHydroquinone >2.5 × E−4  >2.5 × E−4  (CAS# 95-71-6) IC50 is the conc. ofthe candidate that displaces 50% of the radioactive ligand from the rhERcells >2.5 × E4 compounds did not compete to the extent of 50% withradiolabeled 17B-estradiol at the highest conc. (250,000 nM) tested, noIC50 can be determined

The estradiol binding of phenolic compounds seems to be veryunpredictable. It does not correlate with molecular weight, phenolicgroup separation, molecular rigidity, solubility, steric or electroniceffects. Note that while the phenolic compounds of our invention show nodisplacement at the alpha or beta estradiol binding sites atconcentration below the 2.5×E-4M limit of detection, even the controlexamples, while showing some binding, are not as reactive as estradiol(control examples A, H and M). 17b-Estradiol binds at a very lowconcentration.

Polyetherimide Preparation & Testing

Procedure for Dianhydride Preparation.

Under a nitrogen atmosphere, a mixture of (1 mol) of the disodium saltof the bisphenols: bis-(4-hydroxyphenyl)-N-phenyl phenolphthalein or2,2′6′6′-tetramethyl bisphenol A and 4-fluorophthalic anhydride (2 mol)were dissolved in dried DMAC (dimethyl acetamide) and heated at 180° C.The solution became homogeneous after 5 to 10 min. The solution wasstirred for a total of one hour and allowed to cool to room temperature.The reaction mixture was then poured into a mixture of 200 ml of 1Naqueous HCl and ice. The resulting yellow to white precipitate wasfiltered and washed with 50 ml of water and then methanol to give 80 to85% of the desired dianhydride shown in the figures below. Thedianhydrides were recrystallized in acetic acid and acetic anhydriderespectively resulting in pure compounds (50 to 55% yield).

Polymerization Procedure.

In a typical experiment a 25 ml test tube was charged with (0.6870 mmol)of dianhydride and (0.6870 mmol) of m-phenylenediamine (mPD). To thereaction mixture was added 3.6 g of o-dichlorobenzene (ODCB) as asolvent. The reaction mixture was refluxed at 180° C. for 4 h. After 4h, the reaction mixture was poured into a Teflon coated aluminum foilmade into a tube. The tube was heated in a hot block up to 380° C. for20 min. to remove the solvent yielding the N-phenyl phenolphthalein metaphenylene diamine (mPD) polyetherimide (Example 9) and tetra methyl BPAmPD polyetherimide (Example 10).

Example 9

Example 10

Molecular Weight Analysis by GPC.

Molecular weights were determined by gel permeation chromatography (GPC)analysis with a Waters 2695 Separations Module equipped with a PolymerLabs Pigel 5 μm MIXED-C column and Waters 2487 PDA detector at 254 nm.Elution was effected with isocratic solvent system of dichloromethane at1 mL/min and Mw is reported relative to polystyrene standards obtainedfrom Polymer Labs. Each sample was run for 15 minutes with an injectionvolume of 5 μL.

TGA and DSC Measurements.

Thermal Gravimetric Analysis (TGA) measurements were performed with a TAQ800 TGA. The samples were scanned from 40° C. to 800° C. under nitrogenwith a heating rate of 20° C./min. Differential Scanning calorimetry(DSC) measurements were performed with a TA Q1000 DSC. The samples werescanned from 40° C. to 350° C. under nitrogen atmosphere. The glasstransition temperatures (T_(g)), of the polymers were determined fromthe second heating at the rate of 20° C./min.

Characterization of the polymers of Examples 9 and 10 are shown in Table4. The N-phenyl phenolphthalein (PPPBP) mPD polyetherimde (Example 9)had a Tg of 290° C., the tetra methyl BPA (TMeBPA) polyetherimide mPD(Example 10) had a Tg of 249° C. both considerably above the 217° C. Tgof the bisphenol A (BPA) dianhydride based mPD polyetherimide (controlexample P).

The polymers made from the indicated dianhydride and m-phenylene diaminehad weight average molecular weights (Mw) of 49,800 and 56,800 andnumber average (Mn) molecular weights of 24,300 and 26,800 which wereabove the BPA dianhydride derived polyetherimide control (Table 4).

Thermal gravimetric analyses (TGA) were run in nitrogen to determine thetemperature of peak decomposition. Both the N-phenyl phenolphthalein andtetra methyl BPA polyetherimides show very good resistance todecomposition with a peak rate of decomposition above 500° C. The totalweight loss at 800° C. was less than 60% of the starting polymer weight.

TABLE 4 Polymer Properties peak % wt wt. loss Exam- PEI-MPD GPC GPC Tgloss 800° C. ple Polymer Mw Mn PDI (° C.) in N₂ (N₂) P BPA 38000 177002.15 217 554 49 9 PPPBP 49800 24300 2.05 290 581 45 10 TMeBPA 5680026800 2.12 249 505 55

Examples 11 to 22

A further set of polyetherimides, examples 11 to 22 were prepared fromthe phenolic monomers: di-tert butyl hydroquinone (DTBHQ), methylhydroquinone (MHQ), spiro biindane bisphenol (SBIBP) and N-phenyl phenylphenolphthalein (PPPBP) that show no displacement at the alpha or betaestradiol binding sites at concentration below the 2.5×E-4M. Oneequivalent of the disodium salts of the aforementioned bisphenols wereseparately reacted with two equivalents of 4-fluoro phthalic anhydridefor 1 hr at 170° C. in dimethyl acetamide (DMAC) as described in theprocedure for dianhydride preparation of examples 9 and 10. Theresultant dianhydrides were recovered from solution and purified bymethanol washing and/or recrystallization. The DTBHQ-dianhydride andMHQ-dianhydride were recrystallized from methanol, the SBIBP-dianhydridefrom acetic anhydride and the PPPBP dianhydride from acetonitrile. Thedianhydrides were then polymerized with one equivalent of meta-phenylenediamine (mPD), para-phenylene diamine (pPD) or diamino diphenyl sulfone(SDA) in a solution of DMAC at room temperature for at least 1 hr. tomake an amide acid imide polymer. The 12.5% solids amide acid imidesolutions were fully imidized with removal of DMAC solvent undernitrogen to prepare thin films by gradually heating from 25 to 375° C.The heating schedule to remove solvent and complete imidization is shownin Table 5.

TABLE 5 Film Casting of Amide Acid DMAC Solution Time (min.) 0 45 60 90120 150 165 180 195 225 T ° C. 25 40 40 120 120 160 160 200 200 375

The polyimide films were characterized by: DSC to measure Tg (20° C./minheating rate), % wt. gain after 24 hr. immersion in water at 23° C. andthe onset of weight loss under nitrogen and air by thermo gravimetricanalysis (TGA). Coefficient of thermal expansion (CTE) was measured inppm/° C. by thermo mechanical analyses during heating from −50 to 170°C. The data for the various polyetherimides is shown in Table 6. Thepolyetherimides of examples 11 to 22 all show high heat capability witha glass transition temperature (Tg) above 200° C. Good thermal stabilitywas shown by less than 1% TGA weight loss below 400° C. in either air ornitrogen. A CTE of 36 to 47 ppm/° C. showed good dimensional stability.Moisture absorption is 3.15% or less for all the polyetherimides ofTable 6 with many polymers having 2.65% or less weight gain on immersionin water at 23° C. for 24 hrs. Note that example 20 is a replicate ofexample 9. In this instance the polymers with pPD, examples 12 and 15,were too brittle to allow reliable measurements to be made.

TABLE 6 Polyetherimide Properties Examples 11 to 22 TGA decomp. TGAdecomp. CTE Tg ° C. Temp. ° C. Temp. ° C. % water ppm −50 ExampleComposition (DSC) (N2) (Air) abs to 170° C. 11 DTBHQ-mPD 252 455 4681.47 44.1 12 DTBHQ-pPD 272 490 490 1.25 film too brittle 13 DTBHQ- SDA286 474 485 1.27 47.1 14 MHQ-mPD 253 458 450 2.01 41.3 15 MHQ-pPD not476 462 film too film too detected brittle brittle 16 MHQ-SDA 275 457460 2.12 44.8 17 SBIBP-mPD 265 513 517 1.21 41.3 18 SBIBP-pPD 281 513509 1.47 46.8 19 SBIBP-SDA 285 512 510 1.60 46.2 20 PPPBP-mPD 290 513551 2.65 36.2 21 PPPBP-pPD 305 522 524 2.83 40.9 22 PPPBP-SDA 309 521550 3.15 38.7

What is claimed is:
 1. A method of producing an article having lowestradiol binding activity comprising, identifying an article for whichestradiol binding activity is to be low, selecting one or more phenolicmonomers from di-t-butyl hydroquinones and bis-(hydroxy aryl)-N-arylisoindolinones, or, selecting at least two phenolic monomers from oneof: (a) di-t-butyl hydroquinone, spiro biindane bisphenols, resorcinol,hydroquinone, methyl hydroquinone, and biphenols; (b) di-t-butylhydroquinone, spiro biindane bisphenols, hydroquinone, and biphenols;(c) di-t-butyl hydroquinone, spiro biindane bisphenols, methylhydroquinone, and biphenols; (d) di-t-butyl hydroquinone, spiro biindanebisphenols, resorcinol, hydroquinone, methyl hydroquinone, andtetramethyl bisphenol-A; (e) di-t-butyl hydroquinone, spiro biindanebisphenols, hydroquinone, and tetramethyl bisphenol-A; and, (f)di-t-butyl hydroquinone, spiro biindane bisphenols, methyl hydroquinone,and tetramethyl bisphenol-A; wherein each of said monomers do notexhibit a half maximal inhibitory concentration (IC50) less than0.00025M for alpha or beta in vitro estradiol receptors, andmanufacturing the article with a polyetherimide composition comprisingrepeating units derived from the one or more phenolic monomers, andwherein one or more residual phenolic monomers are present at more thanzero but less than or equal to 1,000 ppm and do not exhibit a halfmaximal inhibitory concentration (IC50) less than 0.00025M for alpha orbeta in vitro estradiol receptors.
 2. The method of claim 1, wherein thepolyetherimide is end capped with phenol.
 3. The method of claim 1,wherein the polyetherimide is a co-polyetherimide comprising repeatingunits derived from the two or more phenolic monomers.
 4. The method ofclaim 1, wherein the polyetherimide composition further comprises one ormore additives and wherein each of the one or more additives does notexhibit a half maximal inhibitory concentration (IC50) less than0.00025M for alpha or beta in vitro estradiol receptors.
 5. The methodof claim 4, wherein the one or more additive comprises a stabilizer,antioxidant, colorant, impact modifier, flame retardant, anti dripadditive, mold release additive, lubricant, plasticizer, mineral,reinforcement additive, or any combination thereof.
 6. The method ofclaim 4, wherein the one or more additive comprises a phosphite andwherein when the phosphite, phosphonate or mixture thereof is subjectedto conditions effective to provide one or more phosphite, or phosphonatehydrolysis product, each of the one or more phosphite or phosphonatehydrolysis products does not exhibit a half maximal inhibitoryconcentration (IC50) less than 0.00025M for alpha or beta in vitroestradiol receptors.
 7. The method of claim 6, wherein the phosphitecomprises a diphenyl alkyl phosphite, phenyl dialkyl phosphite, trialkylphosphite, dialkyl phosphite, triphenyl phosphite, diphenylpentaerythritol diphosphite, or any combination thereof.
 8. The methodof claim 6, wherein the phosphite has a Mw greater than 200 Daltons. 9.The method of claim 1, wherein the polyetherimide composition furthercomprises: a) a Mw in the range of from 3,000 to 80,000 Daltons; b) aphenolic end group content less than 20 meq/kg; c) a chloride contentless than 1000 ppm; and d) a transition metal content less than 20 ppm;and wherein the one or more residual phenolic monomers are present atmore than zero but less than 100 ppm.
 10. The method of claim 1, whereinthe polyetherimide composition has a Tg from 200 to 320° C., a weightgain on immersion in water for 24 hours at 23° C. of less than 3.5%, anda coefficient of expansion from 30 to 50 ppm/° C.
 11. The method ofclaim 1, wherein the article is manufactured by injection molding. 12.The method of claim 1, wherein the article is a food service article, amedical use article, or a personal electronics article.
 13. The methodof claim 12, wherein the article is a drinking glass, a bottle, asyringe, a tray, a handle, a computer enclosure, or a cell phonehousing.
 14. The method of claim 1, wherein the article is a pitcher, aconnector, a filter housing, a pipe, a keycap, a film, or a coating. 15.A method of producing a handle or tray having low estradiol bindingactivity comprising, selecting one or more phenolic monomers fromdi-t-butyl hydroquinones and bis-(hydroxy aryl)-N-aryl isoindolinones,or, selecting at least two phenolic monomers from one of: (a) di-t-butylhydroquinone, spiro biindane bisphenols, resorcinol, hydroquinone,methyl hydroquinone, and biphenols; (b) di-t-butyl hydroquinone, spirobiindane bisphenols, hydroquinone, and biphenols; (c) di-t-butylhydroquinone, spiro biindane bisphenols, methyl hydroquinone, andbiphenols; (d) di-t-butyl hydroquinone, spiro biindane bisphenols,resorcinol, hydroquinone, methyl hydroquinone, and tetramethylbisphenol-A; (e) di-t-butyl hydroquinone, spiro biindane bisphenols,hydroquinone, and tetramethyl bisphenol-A; and, (f) di-t-butylhydroquinone, spiro biindane bisphenols, methyl hydroquinone, andtetramethyl bisphenol-A; wherein each of said monomers do not exhibit ahalf maximal inhibitory concentration (IC50) less than 0.00025M foralpha or beta in vitro estradiol receptors, and manufacturing the handleor tray with a polyetherimide composition comprising repeating unitsderived from the one or more phenolic monomers, and wherein one or moreresidual phenolic monomers are present at more than zero but less thanor equal to 1,000 ppm and do not exhibit a half maximal inhibitoryconcentration (IC50) less than 0.00025M for alpha or beta in vitroestradiol receptors.
 16. The method according to claim 1, wherein thephenolic monomers in the polyetherimide composition consist of theselected phenolic monomers.
 17. The method according to claim 15,wherein the phenolic monomers in the polyetherimide composition consistof the selected phenolic monomers.